The Involvement of Cytochrome c Oxidase in Mitochondrial Fusion in Primary Cultures of Neonatal Rat Cardiomyocytes

The Involvement of Cytochrome c Oxidase in Mitochondrial Fusion in Primary Cultures of Neonatal...
Yin, Wen; Li, Rui; Feng, Xiaorong; James Kang, Y.
2018-02-02 00:00:00
Cytochrome c oxidase (CCO) is a copper-dependent enzyme of mitochondrial respiratory chain. In pressure overload-induced cardiac hypertrophy, copper level and CCO activity are both depressed, along with disturbance in mitochondrial fusion and fission dynamics. Copper repletion leads to recovery of CCO activity and normalized mitochondrial dynamics. The present study was undertaken to define the link between CCO activity and mitochondrial dynamic changes. Primary cultures of neonatal rat cardiomyocytes were treated with phenylephrine to induce cell hypertrophy. Hypertrophic cardiomyocytes were then treated with copper to reverse hypertrophy. In the hypertrophic cardiomyocytes, CCO activity was depressed and mitochondrial fusion was suppressed. Upon copper repletion, CCO activity was recovered and mitochondrial fusion was reestablished. Depression of CCO activity by siRNA targeting CCO assembly homolog 17 (COX17), a copper chaperone for CCO, led to fragmentation of mitochondria, which was not recoverable by copper supplementation. This study thus demonstrates that copper-dependent CCO is critical for mitochondrial fusion in the regression of cardiomyocyte hypertrophy.
http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.pngCardiovascular ToxicologySpringer Journalshttp://www.deepdyve.com/lp/springer-journals/the-involvement-of-cytochrome-c-oxidase-in-mitochondrial-fusion-in-7tTTabcSRt

The Involvement of Cytochrome c Oxidase in Mitochondrial Fusion in Primary Cultures of Neonatal Rat Cardiomyocytes

Abstract

Cytochrome c oxidase (CCO) is a copper-dependent enzyme of mitochondrial respiratory chain. In pressure overload-induced cardiac hypertrophy, copper level and CCO activity are both depressed, along with disturbance in mitochondrial fusion and fission dynamics. Copper repletion leads to recovery of CCO activity and normalized mitochondrial dynamics. The present study was undertaken to define the link between CCO activity and mitochondrial dynamic changes. Primary cultures of neonatal rat cardiomyocytes were treated with phenylephrine to induce cell hypertrophy. Hypertrophic cardiomyocytes were then treated with copper to reverse hypertrophy. In the hypertrophic cardiomyocytes, CCO activity was depressed and mitochondrial fusion was suppressed. Upon copper repletion, CCO activity was recovered and mitochondrial fusion was reestablished. Depression of CCO activity by siRNA targeting CCO assembly homolog 17 (COX17), a copper chaperone for CCO, led to fragmentation of mitochondria, which was not recoverable by copper supplementation. This study thus demonstrates that copper-dependent CCO is critical for mitochondrial fusion in the regression of cardiomyocyte hypertrophy.

Journal

Cardiovascular Toxicology
– Springer Journals

Published: Feb 2, 2018

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References

Structure and function of bacterial cytochrome c oxidase

Iwata, S

Structure of cytochrome c oxidase: A comparison of the bacterial and mitochondrial enzymes